Malaria is a leading cause of human death and illness, causing each year 400-600 million cases of clinical malaria and 2-3 million deaths. Traditional measures to control and cure malaria are becoming increasingly neffective, and there is an urgent need for the development of new drugs and vaccines. Genomic studies and other hi-tech advances have produced a wealth of information about malaria parasites, yet using this information for functional analysis of the Plasmodium genome is hindered by a limited capability to genetically manipulate malaria parasites. We are developing technology for high throughput whole-genome mutagenesis screening of malaria parasites, using an efficient transposon-based method for parasite transformation. We propose developing this system for large-scale transposon mutagenesis of Plasmodium falciparum with the long-term goal of enhancing our understanding the genetic basis of the biology the malaria parasite, and greatly accelerating efforts to develop new therapies.